SUMMARY - HEALTHSPAN AND FUNCTIONAL ASSESSMENT CORE The Healthspan and Functional Assessment Core (Healthspan Core) supports the overall mission of the San Antonio (SA) Nathan Shock Center to enable research that will expand our understanding of mechanisms of aging and of age-associated disease, in order to accelerate the development of novel strategies and the identification of (pharmacological) targets to extend healthy life extectancy. The Core provides services to the scientific community on the selection, design, and performance of a wide array of functional assays in mice, rats, and now also in naked mole-rats and marmosets, to elucidate mechanisms that control age-related changes in function at the tissue, organ, and whole body levels in the context of normal aging and in relation to age-related diseases. The Core measures bioenergetics and metabolism, mitochondrial function, body composition, exercise function/tolerance, cardiovascular function, muscle strength/contractility/fatigue, locomotor and neuromotor function, and cognitive/brain health in mice, rats, naked mole-rats and marmoset models, and tests/validates and develops innovative measures of resilience and frailty in both mice and marmosets. Since its creation in 2010, the Healthspan Core has served 21 investigators, many repeat users, and contributed to 50 publications and 19 funded plus 6 pending grant proposals. Examples of discoveries made with support from the Healthspan Core include the first demonstration of mechanisms of maintenance of cardiac function during aging in naked mole-rats; a genetic demonstration of the inverse relationship between insulin sensitivity and longevity in mice; the first studies demonstrating beneficial immune, cognitive, and vascular effects of TOR inhibition by rapamycin, the first drug proven to extend lifespan in mammals; and the first demonstration that rapamycin can be administered efficaciously to marmosets. The Healthspan Core will build on its successful track record, supported by the expertise of investigators who have led the Core since its inception. The Specific Aims of the Healthspan Core are: 1) To assist investigators with the design of experiments and the selection of tests to measure age-associated functional changes; 2) To carry out functional assessments, data collection and analyses; 3) To test and validate measures of frailty in mice and develop novel resilience/frailty measures in marmosets; 4) To expand the impact of the Core through education of researchers on concepts and tools of the field and through hands-on training. The Healthspan Core will contribute to the Center's mission to facilitate transformative research in aging biology through a comprehensive research platform that is unique in the aging research community, able to longitudinally study and integrate longevity (lifespan), physiological (healthspan), pathological, and molecular phenotypes. By the end of the funding cycle, we expect that the Core will have significantly contributed to the identification of novel molecular and cellular mechanisms that influence aging, consequently enabling the development of novel strategies and (pharmacological) targets to extend healthy lifespan.